Novel pyridylpropyl thiocarbonates: insect repellents

Description

[0001] This invention relates to novel compounds having the formula

in which R is selected from the group consisting of alkyl having a saturated straight or branched chain of 1 to 20 carbon atoms, saturated cycloalkyl having 3 to 7 carbon atoms, phenyl which is bonded to an aliphatic straight or branched chain of 1 to 3 carbon atoms, chlorophenyl and chlorobenzyl, and in which R¹ is hydrogen or an alkyl radical having a saturated straight or branched chain of 1 to 4 carbon atoms and n is 1, 2 or 3.

[0002] If R₁ is hydrogen, according to an embodiment of the invention, the side chain may be substituted on the pyridine ring at the 2-, 3-, or 4-position; if R₁ is an alkyl radical having 1 to 4 carbon atoms, according to another embodiment of the invention the side chain may be substituted on the 2-position. If R is an alkyl radical it comprises preferably 1 to 12 carbon atoms. An example for a cycloalkyl radical is cyclohexyl. If R is aralkyl, it comprises preferably 1 or 2 carbon atoms, for instance, benzyl and phenethyl.

[0003] The compounds have utility as insect repellents, particularly for repelling flying insects from lighting and/or feeding.

[0004] The compounds of this type can be prepared by reaction of an appropriate pyridyl alkanol with an appropriate chlorothioformate;

[0005] The pyridyl alkanols in which R is lower alkyl, if not commercially available, can be synthesized, for example, by the method of Umezawa et al., Japanese Patent Application 74/13180.

[0006] The reaction is generally conducted at temperatures of about 0°C to about 25°C. in the presence of a solvent such as methylene chloride and a hydrogen chloride acceptor such as sodium bicarbonate, triethylamine, or pyridine. The product is recovered by conventional extraction, washing, filtration, and other purification steps as may be necessary. Optionally, the hydrogen chloride acceptor may be added after the reaction has gone to completion.

[0007] Preparation of such compounds is illustrated by the following example.

Preparation of S-methyl, O-[3-(3-pyridyl)-1-propyl] Thiocarbonate

(Compound 1 herein)

[0008] In a flask were placed 5.0 grams (g.) (0.0364 mole) 3-(3-pyridyl)-1-propanol and 50 milliliters (ml.) methylene chloride. The flask was cooled to 0°C. There was then added, with stirring, 4.4 g (0.04 mole) methyl chlorothioformate, at such a rate as to maintain the temperature at a maximum of 15°C. After addition was complete, the mixture was stirred for 1 hour at room temperature.

[0009] The product was neutralized with saturated sodium bicarbonate, then washed with water and saturated sodium chloride, and dried over sodium sulfate. The dried solution was filtered and the solvent removed in vacuo, producing 6.2 g. (82% of theoretical yield) of the desired product, a clear, yellow oil, no 1.5335. The structure of the product was confirmed by infrared (ir), nuclear magnetic resonance (nmr) and mass spectroscopy (ms).

[0010] The following Table I contains a list of representative compounds of this invention.

[0011] The structures of the compounds in the foregoing Table I were confirmed by ir, nmr, and/or ms.

Insect Repellent Tests

[0012] Compounds described in the above Table I were tested for insect repellency by the following procedures:

Mosquitoes

[0013] A paper cup filled with pupae of the mosquito Culex pipiens quinquefasciatus (Say) was placed in a screened cage and the pupae allowed to emerge into adults. Sugar cubes were then saturated with 1.0 milliliter (ml.) of an acetone solution containing 0.1 wt.% of the test compound, and, for a control, with the same amount of acetone alone. After the cubes dried they were put into the screened cage. Repellency was determined by the number of mosquito adults lighting and feeding on the sugar cubes, with observations being made daily for 5 days after treatment. The number of days of complete repellency of mosquitoes from the sugar cubes was recorded.

[0014] Comparative tests were similarly conducted using the compound N,N-diethyl-m-toluamide, commercially manufactured and employed as an insect repellent, generally known by the generic name "deet". The results of the tests of deet and the compounds of Table I are shown in the following Table II. The numbers of each column represent the number of days of complete repellency observed using the specified concentration.

Houseflies

[0015] The insect utilized for this test was the housefly, Musca domestica (L.). One hundred houseflies of mixed sexes were placed in test cages. In each cage was placed a sugar cube saturated with 1.0 ml of acetone containing 1 wt.% of the test compound. The cube was dried and weighed before being placed in the cage. Each cage also contained a water-saturated cotton plug, to provide moisture. The test cages were placed on a turntable and rotated at 1.5 revolutions per minute to keep the flies randomly distributed inside the cage. After 48 hours the flies in each cage were anesthetized with carbon dioxide. The sugar cubes were removed and reweighed and the percentage weight loss (due to consumption by the flies) recorded. A repellency ratio, calculated as the percent weight loss of the treated sugar cube divided by the percent weight loss of a control sugar cube treated with acetone only was calculated. The lower the repellency ratio, the greater the repellency of the test compound. The repellency ratios of the test compounds are shown in the following Table III. Values given for the repellency ratio represent an average of from one to three replications per compound.

[0016] Thus at a concentration of 1% by weight, the test compounds repelled insects to the extent that the weight loss of sugar cubes treated with those compounds was generally less than 50% of that of the control (untreated) cubes.

Stable F/y; Yellow Fever Mosquito

[0017] Insects utilized for these tests were the stable fly, Stomoxys calcitrans and yellow fever mosquito, Aedes aegypti.

[0018] Pupae of these insects were placed in separate standard fly cages and allowed to emerge into adults. The mosquitoes were supplied with a sugar-water solution; the stable flies with water, sugar cubes, and casein. Tests on mosquitoes were performed at least 3 days after the adults emerged; those on stable flies, one day after emergence because of the short life span (4-5 days) of these flies without a blood meal.

[0019] Test compounds were weighed and dissolved in acetone. One milliliter (ml) of the test solution was pipetted onto a 9 x 9 cm. swatch of cotton stocking. The swatches were then allowed to dry for 1 hour.

[0020] A square opening 6 x 6 cm. was made in an upper corner of one side of each fly cage. A large, hard cardboard disk was placed over the opening so that it could be rotated to either cover or expose the opening as desired. One-half of the disc was left intact. In the remaining half, several 6 x 6 cm. square openings were cut. When the intact half of this disc was located over the opening in the fly cage, this opening was effectively sealed.

[0021] Swatches of treated stocking were placed over the square holes in the disc and held in place by metal frames attached to magnetic tape.

[0022] To initiate the test, the disc was rotated so that a treated swatch became located over the opening in the cage. The palm of the tester's hand was placed over a cardboard ring, 8 cm. in diameter and 1 cm. thick. The ring acted as a spacer and protected the hand from bites which could otherwise by inflicted by the insects. A breath of air was exhaled through tubing into the opening, so that insects could be attracted to the swatch by the warm, moist air and the tester's hand. The number of insects landing on the swatch was observed, and the number probing, recorded during a 1-minute exposure. Repellency was considered to occur when 5 or-fewer insects probed the swatch during the exposure.

[0023] The compounds were tested at applications rates ranging from 0.1 mg/cm² of swatch downwards. The resuits of these tests on stable flies (SF) and yellow fever mosquitoes (YFM) are contained in Table IV.

Black Blowfly, Housefly

[0024] Compounds 1 and 2 were tested for repellent activity against the black blowfly, Phormia regina and the hornfly, Haematobia irritans. The blowfly tests were conducted similarly to those on the housefly; the hornfly tests were conducted similarly to those on the stable fly. Results are reported in Table V below.

[0025] The novel compounds of this invention may be used as insect repellents in either diluted or undiluted form. When used in a diluted form, the compounds may be embodied in compositions containing relatively high or relatively low concentrations of the active compound. For example, the active compound can be incorporated into relatively high concentration compositions such as wet sprays or solutions in alcohol or other suitable solvents. Such compositions may contain, in addition to the active compound, adjuvants such as emulsifying agents, surface active agents, anti-oxidants and propellants which may be found normally in insect repellent preparations. The active compounds of this invention may be employed as the sole active component of such compositions or may be used in admixture with other compounds having a similar or different utility. For example, the compounds may be incorporated into creams, lotions, powders, suntan oil, insecticides and other preparations which may contain pesticidal or other useful substances, as well as into compositions of various types used for treating fabrics or articles of clothing to render them insect repellent. In general, compositions for repellent use may contain from 0.5 to up to 80 weight %, preferably from 2 to about 40 weight %, of the novel active compounds. High concentration formulations, containing up to 95% of the compounds, could also be utiized for low-volume spraying from the air.

[0026] Examples of typical formulations employing compounds of this invention are for instance,

Example 1: Emulsifiable Concentrate

[0027] 

Example 2: Lotion

[0028] 

Example 3: Alcohol Solution

[0029] 

Example 4: Alcohol Solution

[0030] 

Example 5: Wettable Powder

[0031] 

Example 6: Low Concentration Solution

[0032] 

Example 7: Alcohol Solution

[0033] 

Claims

1. A compound having the formula

in which R is a radical selected from the group consisting of alkyl having a saturated straight or branched chain of 1 to 20 carbon atoms, saturated cycloalkyl having 3 to 7 carbon atoms, phenyl which is bonded to an aliphatic straight or branched chain of 1 to 3 carbon atoms, chlorophenyl and chlorobenzyl, R¹ is hydrogen or an alkyl radical having a saturated straight or branched chain of 1 to 4 carbon atoms and n is 1, 2 or 3.

2. A compound according to Claim 1 in which the side chain is substituted on the pyridine ring at the 2- position.

3. A compound according to Claim 1 in which the side chain is substituted on the pyridine ring at the 3- position.

4. A compound according to any of Claims 1-3 in which R₁ is hydrogen and R is alkyl.

5. A compound according to any of Claims 1-4 in which R is C1-C12 alkyl.

6. A compound according to Claim 1 in which R₁ is hydrogen, R is methyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.

7. A compound according to Claim 1 in which R₁ is hydrogen, R is ethyl, n is 3 and the side chain is substituted on the pyridine ring at the 3-position.

8. A compound according to Claim 1 in which R₁ is hydrogen, R is ethyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.

9. A compound according to Claim 1 in which R₁ is hydrogen, R is isopropyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.

10. A compound according to Claim 1 in which R₁ is hydrogen, R is sec.-butyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.

11. A compound according to Claim 1 in which R₁ is hydrogen, R is isobutyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.

12. A compound according to Claim 1 in which R₁ is hydrogen, R is n-propyl, n is 3 and the side chain is substituted on the pyridine ring at the 2-position.

13. A method of repelling insects from a locus to be protected therefrom, comprising applying to said locus an effective insect repelling amount of a compound according to any of Claims 1-12.

14. A method according to Claim 13 in which the insect is the housefly.

15. A method according to Claim 13 in which the insect is yellow fever mosquito.

16. A method according to Claim 13 in which the insect is stable fly.

17. An insect repellent composition comprising: (a) an amount of a compound according to any of Claims 1-12, effective to repel insects; and (b) an inert diluent or carrier suitable for insect repellent use.

18. A method for production of a compound according to any of Claims 1 to 12 in which a pyridyl alkanol having the formula

in which R is as defined in Claim 1 is reacted with a chlorothioformate having the formula

in which R is as defined in Claim 1 at a temperature of 0 to 25°C, in the presence of a solvent and a hydrogen chloride acceptor.

Ansprüche

1. Stoff mit der Formel

wobei R ein Alkylrest mit einer gesättigten unverzweigten oder verzweigten Kette von 1 bis 20 Kohlenstoffatomen, ein gesättigter Cycloalkylrest mit 3 bis 7 Kohlenstoffatomen, ein an eine aliphatische unverzweigte oder verzweigte Kette von 1 bis 3 Kohlenstoffatomen gebundener Phenylrest, Chlorphenyl oder Chlorbenzyl ist, R¹ Wasserstoff oder ein Alkylrest mit einer gesättigten unverzweigten oder verzweigten Kette von 1 bis 4 Kohlenstoffatomen und n 1, 2 oder 3 ist.

2. Stoff nach Anspruch 1, wobei die Seitenkette sich in 2-Stellung des Pyridinringes befindet.

3. Stoff nach Anspruch 1, wobei sich die Seitenkette in 3-Stellung am Pyridinring befindet.

4. Stoff nach einem der Ansprüche 1 bis 3, wobei R, Wasserstoff und R ein Alkylrest ist.

5. Stoff nach einem der Ansprüche 1 bis 4, wobei R C₁ bis C₁₂ Alkyl ist.

6. Stoff nach Anspruch 1, wobei R₁ Wasserstoff, R Methyl, n 3 ist und sich die Seitenkette am Pyridinring in 3-Stellung befindet.

7. Stoff nach Anspruch 1, wobei R, Wasserstoff, R Ethyl, n 3 ist und sich die Seitenkette am Pyridinring in 3-Stellung befindet.

8. Stoff nach Anspruch 1, wobei R₁ Wasserstoff, R Ethyl, n 3 ist und sich die Seitenkette am Pyridinring in 2-Stellung befindet.

9. Stoff nach Anspruch 1, wobei R₁ Wasserstoff, R Isopropyl, n 3 ist und sich die Seitenkette am Pyridinring in 2-Stellung befindet.

10. Stoff nach Anspruch 1, wobei R₁ Wasserstoff, R sek.-Butyl, n 3 ist und sich die Seitenkette am Pyridinring in 2-Stellung befindet.

11. Stoff nach Anspruch 1, wobei R₁ Wasserstoff, R Isobutyl, n 3 ist und die Seitenkette sich am Pyridinring in 2-Stellung befindet.

12. Stoff nach Anspruch 1, wobei R₁ Wasserstoff, R n-Propyl, n 3 ist und sich die Seitenkette am Pyridinring in 2-Stellung befindet.

13. Verfahren zum Schutz eines Ortes gegen Insekten, wobei an jenem Ort ein Stoff nach einem der Ansprüche 1 bis 12 in einer zur Erzielung einer Insektenschutzwirkung ausreichenden Menge angewandt wird.

14. Verfahren nach Anspruch 13, wobei das Insekt die Stubenfliege ist.

15. Verfahren nach Anspruch 13, wobei das Insekt die Gelbfiebermücke ist.

16. Verfahren nach Anspruch 13, wobei das Insekt die Gemeine Stechfliege ist.

17. Schutzmittel gegen Insekten aus (a) einem Stoff nach einem der Ansprüche 1 bis 12 in einer zur Erzielung einer Schutzwirkung gegen Insekten ausreichenden Menge und (b) einem inerten Verdünnungsmittel oder Trägermaterial, das zur Verwendung in einem Schutzmittel gegen Insekten geeignet ist.

18. Verfahren zur Herstellung eines Stoffes nach einem der Ansprüche 1 bis 12, wobei ein Pyridylalkohol mit der Formel

in der R¹ die in Anspruch 1 angegebene Bedeutung hat mit einem Chlorthioformat mit der Formel

in der R die in Anspruch 1 angegebene Bedeutung hat, umgesetzt wird bei einer Temperatur von 0―25°C in Gegenwart eines Lösungsmittels und eines Chlorwasserstoffakzeptors.

Revendications

1. Un composé de formule:

dans laquelle:

R représente un radical choisi dans lé groupe constitué par un radical alkyle possédant une chaîne droite ou ramifiée saturée de 1 à 20 atomes de carbone, cycloalkyle saturé renfermant de 3 à 7 atomes de carbone, phényle qui est lié à une chaîne aliphatique droite ou ramifiée de 1 à 3 atomes de carbone, chloro- phényle et chlorobenzyle;

R¹ représente un atome d'hydrogène ou un radical alkyle renfermant une chaîne saturée droite ou ramifiée de 1 à 4 atomes de carbone; et

n est égal à 1, 2 ou 3.

2. Un composé selon la revendication 1, dans lequel la chaîne latérale est substituée sur le cycle pyridinique en position 2.

3. Un composé selon la revendication 1, dans lequel la chaîne latérale est substituée sur le cycle pyridinique en position 3.

4. Un composé selon l'une quelconque des revendications 1 à 3, dans lequel R₁ représente un atome d'hydrogène et R représente un radical alkyle.

5. Un composé selon l'une quelconque des revendications 1 à 4, dans lequel R représente un radical alkyle en Ci à C₁₂.

6. Un composé selon la revendication 1, dans lequel R₁ représente un atome d'hydrogène, R représente un radical méthyle, n est égal à 3 et la chaîne latérale est substituée sur le cycle de la pyridine en position 3.

7. Un composé selon la revendication 1, dans lequel R₁ représente un atome d'hydrogène, R représente un radical éthyle, n est égal à 3 et la chaîne latérale est substituée sur le cycle de la pyridine en position 3.

8. Un composé selon la revendication 1, dans lequel R₁ représente un atome d'hydrogène, R représente un radical éthyle, n est égal à 3 et la chaîne latérale est substituée sur le cycle de la pyridine en position 2.

9. Un composé selon la revendication 1, dans lequel R₁ représente un atome d'hydrogène, R représente un radical isopropyle, n est égal à 3 et la chaîne latérale est substituée sur le cycle de la pyridine en position 2.

10. Un composé selon la revendication 1, dans lequel R₁ représente en atome d'hydrogène, R représente un radical sec.-butyle, n est égal à 3 et la chaîne latérale est substituée sur le cycle de la pyridine en position 2.

11. Un composé selon la revendication 1, dans lequel R₁ représente un atome d'hydrogène, R représente un radical isobutyle, n est égal à 3 et la chaîne latérale est substituée sur le cycle de la pyridine en position 2.

12. Un composé selon la revendication 1, dans lequel R₁ représente un atome d'hydrogène, R représente un radical n-propyle, n est égal à 3 et la chaîne latérale est substituée sur le cycle de la pyridine en position 2.

13. Procédé d'éloignement des insectes dans un lieu à protéger, qui consiste à appliquer en ce lieu une quantité efficace pour éloigner les insectes d'un composé selon l'une quelconque des revendications 1 à 12.

14. Procédé selon la revendication 13, dans lequel l'insecte est la mouche domestique.

15. Procédé selon la revendication 13, dans lequel l'insecte est le moustique de la fièvre jaune.

16. Procédé selon la revendication 13, dans lequel l'insecte est la mouche d'étable.

17. Composition d'éloignement des insectes, comprenant:

(a) une quantité d'un composé selon l'une quelconque des revendications 1 à 12, efficace pour repousser les insectes; et

(b) un diluant ou support inerte pouvant être utilisé dans l'éloignement des insectes.

18. Procédé de préparation d'un composé selon l'une quelconque des revendications 1 à 12, dans lequel on fait réagir un pyridylalkanol de formule:

dans laquelle R est tel que défini dans la revendication 1, avec un chlorothioformiate de formule:

dans laquelle R est tel que défini dans la revendication 1, à une température de 0 à 25°C, en présence d'un solvant et d'un accepteur d'acide chlorhydrique.